Candidate's Statement: The candidate has extensive training and research experience in women's health, endocrinology, and epidemiology. Her immediate goals are to expand her field of expertise into neuroscience and genetic epidemiology and to solidify her training in clinical research. Ultimately, she wants to launch an independent research career in the field of sex hormones and the menopause. To accomplish her goals, she will attend formal and informal didactics in neuroscience, genetics, and clinical research and implement the studies described under the research section. Environment: Oregon Health Sciences University (OHSU) is the only medical school in the state, and has a strong tradition of research and training. This study will utilize the OHSU General Clinical Research Center, which is a 12,500 square foot facility that includes a Core Laboratory (with a wide array of analytical instruments including specialized genetics equipment), bionutrition unit, and computing center. Research Project: The overall goal is to characterize the hormonal, cognitive, and somatic changes that occur during the menopausal transition and during estrogen supplementation. In Aim 1, we will conduct an observational study of perimenopausal women to determine the relationship between symptoms, sleep, mood, and cognition and estradiol levels and change in estradiol levels. In Aim 2, we will perform a randomized controlled trial to differentiate whether the changes in cognition, sleep, and mood that occur with estrogen replacement are due to menopausal symptom relief. In Aim 3, we will seek associations between protein variants (functional gene sequence variations) involved in estradiol synthesis and metabolism and action and menopausal events (including estradiol levels, symptoms, sleep, mood, cognition, and response to estrogen supplementation).